Fig. 3: Edition of mutant KRAS induces tumor growth inhibition in PDX and CDXs models. | Nature Communications

Fig. 3: Edition of mutant KRAS induces tumor growth inhibition in PDX and CDXs models.

From: High-fidelity Cas9-mediated targeting of KRAS driver mutations restrains lung cancer in preclinical models

Fig. 3

A Schematic representation of experimental design with representative ex vivo images of tumors harvested 60 days after implantation. 106 pretreated cells were transplanted subcutaneously and tumor growth was monitored for two months. Representative images of n = 9. B Quantification of ex vivo tumor volumes of H358 (Adv-Control, n = 9; Adv-HiFiCas9, n = 7) and A427 (Adv-Control, n = 8; Adv-HiFiCas9, n = 8) CDXs. 63% reduction in tumor volume for H358 (left; p-value: 0.00017) and a ~ 42% reduction for A427 (right; p-value: 0.015). Boxplots display the median (50th percentile, center line), the 25th and 75th percentiles (lower and upper box bounds, respectively), and the whiskers extend to the smallest and largest values within 1.5 times the interquartile range (IQR) from the lower and upper quartiles. C Schematic representation of PDX experimental design. D Tumor volumes of LU5245 (G12C; Adv-Control, n = 6; Adv-HiFiCas9, n = 6) and LU5162 (G12D, Adv-Control, n = 4; Adv-HiFiCas9, n = 4) PDXs. Mean tumor volume (mm3) normalized to day 1, accompanied by standard deviation. Tumor growth was modeled using a linear mixed-effects model with random intercepts. E Ex vivo pictures from KRASG12C tumors extracted 28 days post-treatment. Scale bar=10 mm. Diameters (mm): PDX1: Control=14, HiFiCas9 = 11; PDX2: Control=13.6, HiFiCas9 = 11.8. Volumes (mm3): PDX1: Control=1084, HiFi-Cas9 = 548; PDX2: Control=948, HiFi-Cas9 = 658. Source data for panels B and D are provided in the Source Data file.

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